The overall objective of this grant is to define the adaptive changes in blood-brain barrier (capillary endothelium) function that occur in central nervous system tumors and other pathological conditions affecting the nervous system. This will be accomplished, by utilizing a technique that simultaneously measures regional cerebral blood flow and extraction of certain sugars, amino acids, and ketone bodies in transit through the cerebral capillary bed, and relating such changes in the kinetic parameters with changes in the morphology of the cerebral capillary. The major emphasis will be those changes that occur in the anatomy and physiology of the blood-brain barrier in a transplanted gliosarcoma in rat brain. The basic changes in the transport capabilities of the barrier under these conditions, as well as the effect of radiation, thermal energy, and chemotherapy will be studied. It is believed that an understanding of these changes, both in neoplastic and non-neoplastic pathological conditions, will allow experimental manipulation of the transformed blood-brain and blood-tumor barrier with subsequent interference with brain-tumor survival, the latter effect being due to alterations in the availability of metabolic substrates required for tumor metabolism.